Ignite Creation Date:
2024-05-06 @ 12:05 AM
Last Modification Date:
2024-10-26 @ 10:44 AM
Study NCT ID:
NCT01486615
Status:
COMPLETED
Last Update Posted:
2012-10-05
First Post:
2011-11-10
Brief Title:
Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone
Sponsor:
BP Koirala Institute of Health Sciences
Organization:
BP Koirala Institute of Health Sciences
Study Overview
Official Title:
Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone a Randomized Double Blind Placebo Controlled Study
Status:
COMPLETED
Status Verified Date:
2012-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background Benzodiazepine a common premedicant suppresses endogenous melatonin levels and thus paradoxically increases episodes of arousal during sleep and thus causes restlessness and hangs over effects Adding melatonin to it may decrease nocturnal arousal and promote the perception of sound sleep in the perioperative period
Methods Eighty patients ASA 12 with anxiety VAS 2 posted for general anaesthesia will be randomly assigned to receive 05 mg alprazolam Group A 3 mg melatonin a combination of 05 mg alprazolam and 3 mg melatonin Group AM or a similar looking placebo Group P approximately 90 minutes before surgery
Methods Eighty patients ASA 12 with anxiety VAS 2 posted for general anaesthesia will be randomly assigned to receive 05 mg alprazolam Group A 3 mg melatonin a combination of 05 mg alprazolam and 3 mg melatonin Group AM or a similar looking placebo Group P approximately 90 minutes before surgery
Detailed Description:
Review of literature
Benzodiazepines are among the most popular drugs used for preoperative medication to produce anxiolysis amnesia and sedation However they negatively influence sleep quality by decreasing the duration of REM sleep and slow wave sleep
Alprazolam is more anxioselective than the more commonly used ones like midazolam lorazepam and diazepamMelatonin N-acetyl-5-methoxytryptamine is an emerging premedicant as it possesses anxiolytic and sedative properties without impairing cognitive or psychomotor skills5 Moreover it has an excellent safety profile
We designed this prospective randomized double blind placebo controlled study to assess whether addition of melatonin to alprazolam has any benefit over alprazolam melatonin or placebo alone as a premedication agent
Rationale of the study Melatonin facilitates sleep onset and improves the quality of sleep On the other hand benzodiazepines suppress endogenous melatonin levels and thus paradoxically increase episodes of arousal during sleep causing restlessness and hang over effects fatigue
Hence the rationale of using melatonin alprazolam combination is melatonin may decrease nocturnal arousal and promote the perception of sound sleep and thus reverse this unwanted side effect of alprazolam Melatonin does not produce amnesia and adding a benzodiazepine to it may be desirable to achieve this desirable premedication effect
Research design and methodology
After getting approval from the institutional research ethics committee and written informed consent we will study eighty patients With the help of computer generated random numbers patients will be assigned to one of the four groups n20 to receive vitamin B Group P 05 mg alprazolam Group A 3mg melatonin Group M or a combination of 05 mg alprazolam and 3 mg melatonin Group AM approximately 90 minutes before surgery In addition to the study drugs Groups A and AM will also receive vitamin B
On the preanaesthetic visit one day prior to surgery the patients will be explained about the nature of the study and the various scales to be used A 10 cm linear Visual Analogue Scale VAS as well as Nepali version of the Amsterdam Preoperative Anxiety and Information Scale APAIS will be used to assess their anxiety level The extremes of the VAS anxiety scale will be marked as no anxiety at the 0 end and anxiety as bad as ever can be at the 10 cm end Sedation will be assessed with a 5 point scale 0alert 1arouses to voice 2arouses with gentle tactile stimulation 3arouses with vigorous tactile stimulation 4lack of responsiveness and orientation with a 3 point scale 0none 1orientation in either time or place 2orientation in both To test for the memory recall of 5 different simple pictures and 2 events will be assessed Pictures to be used will be sequentially numbered on the back and their names printed on the front
Approximately 2 hours prior to surgery each patient will be taken to a quiet room Non invasive blood pressure heart rate respiratory rate and SpO2 will be monitored Then picture 1 cup on a plate and 2 fruits will be shown at 10 min before and just prior to the drug administration respectively Patients will be asked to take the study medication orally with 15 ml of plain water according to the group assignment by an investigator not involved in the patient management and data collection thereafter Then anxiety sedation and orientation will be assessed at 15 min 30 min and 1 hour after the drug administration At these time points pictures 3 bird 4 hare and 5 car will also be shown respectively
In the operating room intravenous access will be secured and pethidine 1 mgkg administered Then intravenous lidocaine 20 mg bolus will be administered followed by propofol with infusion pump at 100 ml per hour till responses to verbal command and eyelash reflex are lost Vecuronium 01 mgkg and isoflurane in oxygen will be administered to maintain the adequate depth of anaesthesia After intubation ventilation will be adjusted to maintain normocapnia Incremental doses of pethidine and vecuronium will be administered as needed on the discretion of the investigator blinded to the patients group assignment No other analgesics will be administered After completion of surgery intravenous neostigmine 50 microgramkg and glycopyrrolate 10 microgramkg will be given to reverse muscle paralysis Anaesthesia time induction to emergence will be noted
In the recovery room patients will receive the standard postoperative care including oxygen administration via face mask 6 Lmin and monitoring of heart rate respiratory rate non invasive blood pressure and SpO2 Modified Aldrete score and sedation score will be assessed at 10 min and 30 min after extubation Also the occurrence of nausea vomiting dizziness headache and restlessness will be recorded till 24 hours Vomiting will be managed with ondansetron 4 mg intravenously
The next day the patients will be asked if they recalled the two events being transported to operating room and intravenous cannula being inserted They will also be asked to have a free recall of the five pictures they were shown and the score will represent the numbers of pictures they recalled Then the first five pictures that they were shown will be mixed with next 5 new pictures of a horse shoe bicycle elephant and tiger and they will be asked to recognize those they had already seen The score will represent the number of pictures correctly identified They will also be asked whether they felt that premedication drug is required to relieve anxiety and also whether they would like to receive the same premedication drug in the future
Statistical analysis Data will be tested for normal distribution using Kolmogorov-Smirnov test To identify differences between groups one-way ANOVA will be used for normally distributed continuing data and chi square tests for categorical data If the data is found to be not normally distributed they will be analyzed with nonparametric statistical methods Friedman repeated measures analysis of variance followed by Wilcoxon tests with Bonferroni correction will be used for within-group comparison of values between different time points Kruskal Wallis tests with post hoc multiple comparisons by Mann Whitney U test will be used for the comparison of values between the groups at each time points Parametric data will be expressed as the meanSD and nonparametric data as median interquartile range A p value 005 will be considered significant
Benzodiazepines are among the most popular drugs used for preoperative medication to produce anxiolysis amnesia and sedation However they negatively influence sleep quality by decreasing the duration of REM sleep and slow wave sleep
Alprazolam is more anxioselective than the more commonly used ones like midazolam lorazepam and diazepamMelatonin N-acetyl-5-methoxytryptamine is an emerging premedicant as it possesses anxiolytic and sedative properties without impairing cognitive or psychomotor skills5 Moreover it has an excellent safety profile
We designed this prospective randomized double blind placebo controlled study to assess whether addition of melatonin to alprazolam has any benefit over alprazolam melatonin or placebo alone as a premedication agent
Rationale of the study Melatonin facilitates sleep onset and improves the quality of sleep On the other hand benzodiazepines suppress endogenous melatonin levels and thus paradoxically increase episodes of arousal during sleep causing restlessness and hang over effects fatigue
Hence the rationale of using melatonin alprazolam combination is melatonin may decrease nocturnal arousal and promote the perception of sound sleep and thus reverse this unwanted side effect of alprazolam Melatonin does not produce amnesia and adding a benzodiazepine to it may be desirable to achieve this desirable premedication effect
Research design and methodology
After getting approval from the institutional research ethics committee and written informed consent we will study eighty patients With the help of computer generated random numbers patients will be assigned to one of the four groups n20 to receive vitamin B Group P 05 mg alprazolam Group A 3mg melatonin Group M or a combination of 05 mg alprazolam and 3 mg melatonin Group AM approximately 90 minutes before surgery In addition to the study drugs Groups A and AM will also receive vitamin B
On the preanaesthetic visit one day prior to surgery the patients will be explained about the nature of the study and the various scales to be used A 10 cm linear Visual Analogue Scale VAS as well as Nepali version of the Amsterdam Preoperative Anxiety and Information Scale APAIS will be used to assess their anxiety level The extremes of the VAS anxiety scale will be marked as no anxiety at the 0 end and anxiety as bad as ever can be at the 10 cm end Sedation will be assessed with a 5 point scale 0alert 1arouses to voice 2arouses with gentle tactile stimulation 3arouses with vigorous tactile stimulation 4lack of responsiveness and orientation with a 3 point scale 0none 1orientation in either time or place 2orientation in both To test for the memory recall of 5 different simple pictures and 2 events will be assessed Pictures to be used will be sequentially numbered on the back and their names printed on the front
Approximately 2 hours prior to surgery each patient will be taken to a quiet room Non invasive blood pressure heart rate respiratory rate and SpO2 will be monitored Then picture 1 cup on a plate and 2 fruits will be shown at 10 min before and just prior to the drug administration respectively Patients will be asked to take the study medication orally with 15 ml of plain water according to the group assignment by an investigator not involved in the patient management and data collection thereafter Then anxiety sedation and orientation will be assessed at 15 min 30 min and 1 hour after the drug administration At these time points pictures 3 bird 4 hare and 5 car will also be shown respectively
In the operating room intravenous access will be secured and pethidine 1 mgkg administered Then intravenous lidocaine 20 mg bolus will be administered followed by propofol with infusion pump at 100 ml per hour till responses to verbal command and eyelash reflex are lost Vecuronium 01 mgkg and isoflurane in oxygen will be administered to maintain the adequate depth of anaesthesia After intubation ventilation will be adjusted to maintain normocapnia Incremental doses of pethidine and vecuronium will be administered as needed on the discretion of the investigator blinded to the patients group assignment No other analgesics will be administered After completion of surgery intravenous neostigmine 50 microgramkg and glycopyrrolate 10 microgramkg will be given to reverse muscle paralysis Anaesthesia time induction to emergence will be noted
In the recovery room patients will receive the standard postoperative care including oxygen administration via face mask 6 Lmin and monitoring of heart rate respiratory rate non invasive blood pressure and SpO2 Modified Aldrete score and sedation score will be assessed at 10 min and 30 min after extubation Also the occurrence of nausea vomiting dizziness headache and restlessness will be recorded till 24 hours Vomiting will be managed with ondansetron 4 mg intravenously
The next day the patients will be asked if they recalled the two events being transported to operating room and intravenous cannula being inserted They will also be asked to have a free recall of the five pictures they were shown and the score will represent the numbers of pictures they recalled Then the first five pictures that they were shown will be mixed with next 5 new pictures of a horse shoe bicycle elephant and tiger and they will be asked to recognize those they had already seen The score will represent the number of pictures correctly identified They will also be asked whether they felt that premedication drug is required to relieve anxiety and also whether they would like to receive the same premedication drug in the future
Statistical analysis Data will be tested for normal distribution using Kolmogorov-Smirnov test To identify differences between groups one-way ANOVA will be used for normally distributed continuing data and chi square tests for categorical data If the data is found to be not normally distributed they will be analyzed with nonparametric statistical methods Friedman repeated measures analysis of variance followed by Wilcoxon tests with Bonferroni correction will be used for within-group comparison of values between different time points Kruskal Wallis tests with post hoc multiple comparisons by Mann Whitney U test will be used for the comparison of values between the groups at each time points Parametric data will be expressed as the meanSD and nonparametric data as median interquartile range A p value 005 will be considered significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None